People With Multiple Sclerosis Treated With Ocrelizumab and GLP-1 Agonists

NCT07207148 | Recruiting FDA Drug

• 1 other identifier: STU00224018
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The primary outcome measure is PIRA (progression independent of relapse activity), based primarily on clinical assessment, dichotomized as present or not. For Aim 1, the cohort, patient-derived disability status (PDDS) score, and ambulation score (self-reported) will be the primary endpoints of interest. For Aim 2, the clinical trial, PIRA will be measured pre-GLP-1 start and at study end (week 72). A composite score of disability, similar to the ORATORIO13 trial will be constructed including EDSS score, 25-foot timed walk, 9-hole peg test, and SDMT score.

Conditions

Multiple Sclerosis

Keywords

Ocrelizumab; GLP-1; Obesity; Weight loss; Progressive MS; Multiple sclerosis; Biomarkers; Weight; Overweight; Neuroprotection; Semaglutide; glucagon-like peptide-1

Outcome Measures

Primary Outcomes (1)

• PIRA

  The primary outcome measure is PIRA (progression independent of relapse activity), based primarily on clinical assessment, dichotomized as present or not.

  From enrollment to the end of study at 72 weeks.

Secondary Outcomes (1)

• Neurofilament light chain

  From the start of Aim 2 to the end of treatment at 72 weeks.

Study Arms (2)

Aim 1

The cohort will implement patient-reported outcome measures (PROMs) in 60 people with MS already treated with both Ocrelizumab and a GLP-1 agonist to assess progression and ambulation, while recording drug tolerability and potential adverse events, weight loss, disease-based outcomes focused on progression, and MS-focused quality of life.

Drug: GLP-1; Drug: Ocrelizumab (US)

Aim 2

The cohort will include a single-arm, open-label trial of 40 Ocrelizumab-treated MS patients who are soon starting GLP-1 agonists, monitored prospectively for 2 years to measure MS progression (clinical disability worsening, stability or improvement) every 3 months, including (a) clinical assessments (e.g. EDSS, 25-foot timed walk, SDMT) as used in the ORATORIO trial of Ocrelizumab, (b) PROMs on progression in MS including fatigue, ambulation distance, mood; and (3) simple objective biomarkers of disease (e.g. plasma neurofilament light chain, glial fibrillary acidic protein).

Drug: GLP-1; Drug: Ocrelizumab (US)

Interventions

GLP-1 DRUG

Glucagon-like peptide-1 agonist agent is the study agent of interest. This study will not supply the GLP-1 drug but depends on the patient's clinical prescription of this drug.

Also known as: Glucagon-like peptide-1, GLP-1 Agonist

Aim 1; Aim 2

Ocrelizumab (US) DRUG

All participants will be treated with Ocrelizumab for the indication of MS; however, the study will not provide Ocrelizumab as it will be part of the participant's routine clinical care.

Also known as: Ocrevus

Aim 1; Aim 2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals with multiple sclerosis already treated with both Ocrelizumab and are either currently on a GLP-1 agonist or who are soon starting a GLP-1 agonist.

You may qualify if:

• Diagnosis of MS (2019 revised McDonald criteria) of any type (PPMS, RRMS, SPMS) by a neurologist,
• Adult age 18-70 years,
• BMI \>=24.0 kg/m2,
• Taken at least one dose of Ocrelizumab prior to study entry,
• EDSS \<7.0,
• Able to provide individual informed consent,
• MRI available to confirm the diagnosis of MS.

You may not qualify if:

• Prior exposure to Mavenclad, Lemtrada, Cyclophosphamide, stem cell transplant or related bone marrow suppressive treatment,
• Current clinical trial participant,
• Unable to speak a language for which translation can be found in the hospital system,
• Unclear documentation of MS diagnosis or prior or current MS treatment,
• Relapse within the past 3 months,
• Recent major surgical procedure in the past 6 months,
• Exposure to steroids (systemic) within the past 3 months,
• Not on Ocrelizumab in the past \>9 months,
• Moribund status,
• Underweight or experiencing protein malnutrition,
• Unable to provide consent voluntarily due to reasons of capacity or other reasons (e.g. incarcerated, dementia, etc.),
• Unable to complete the study activities for any reason as deemed by the study investigator.
• Exposed to GLP-1 agonist treatment in the last 3 years or less, or starting on a GLP-1 agonist in the coming \<3 months,
• Willing to report monthly patient-reported outcomes remotely or in-person.
• Able to present for baseline and follow up in person,

Sponsors & Collaborators

• Northwestern University: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

RECRUITING

Related Publications (14)

• Sharrad D, Chugh P, Slee M, Bacchi S. Defining progression independent of relapse activity (PIRA) in adult patients with relapsing multiple sclerosis: A systematic review✰. Mult Scler Relat Disord. 2023 Oct;78:104899. doi: 10.1016/j.msard.2023.104899. Epub 2023 Jul 20.

  PMID: 37499338 BACKGROUND

• Montalban X, Hauser SL, Kappos L, Arnold DL, Bar-Or A, Comi G, de Seze J, Giovannoni G, Hartung HP, Hemmer B, Lublin F, Rammohan KW, Selmaj K, Traboulsee A, Sauter A, Masterman D, Fontoura P, Belachew S, Garren H, Mairon N, Chin P, Wolinsky JS; ORATORIO Clinical Investigators. Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis. N Engl J Med. 2017 Jan 19;376(3):209-220. doi: 10.1056/NEJMoa1606468. Epub 2016 Dec 21.

  PMID: 28002688 BACKGROUND

• Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983 Nov;33(11):1444-52. doi: 10.1212/wnl.33.11.1444.

  PMID: 6685237 BACKGROUND

• Diz-Chaves Y, Maastor Z, Spuch C, Lamas JA, Gonzalez-Matias LC, Mallo F. Glucagon-like peptide 1 receptor activation: anti-inflammatory effects in the brain. Neural Regen Res. 2024 Aug 1;19(8):1671-1677. doi: 10.4103/1673-5374.389626. Epub 2023 Dec 11.

  PMID: 38103230 BACKGROUND

• Sadek MA, Kandil EA, El Sayed NS, Sayed HM, Rabie MA. Semaglutide, a novel glucagon-like peptide-1 agonist, amends experimental autoimmune encephalomyelitis-induced multiple sclerosis in mice: Involvement of the PI3K/Akt/GSK-3beta pathway. Int Immunopharmacol. 2023 Feb;115:109647. doi: 10.1016/j.intimp.2022.109647. Epub 2022 Dec 28.

  PMID: 36584570 BACKGROUND

• Udawatta M, Fidalgo N, Mateen FJ. Multiple sclerosis patients taking glucagon-like peptide-1 receptor (GLP-1) agonists: a single-institution retrospective cohort study of tolerability and weight loss. Neurol Sci. 2025 Jan;46(1):343-349. doi: 10.1007/s10072-024-07701-7. Epub 2024 Jul 20.

  PMID: 39030327 BACKGROUND

• Li M, Lin H, Yang Q, Zhang X, Zhou Q, Shi J, Ge F. Glucagon-like peptide-1 receptor agonists for the treatment of obstructive sleep apnea: a meta-analysis. Sleep. 2025 Apr 11;48(4):zsae280. doi: 10.1093/sleep/zsae280.

  PMID: 39626095 BACKGROUND

• Meissner WG, Remy P, Giordana C, Maltete D, Derkinderen P, Houeto JL, Anheim M, Benatru I, Boraud T, Brefel-Courbon C, Carriere N, Catala H, Colin O, Corvol JC, Damier P, Dellapina E, Devos D, Drapier S, Fabbri M, Ferrier V, Foubert-Samier A, Frismand-Kryloff S, Georget A, Germain C, Grimaldi S, Hardy C, Hopes L, Krystkowiak P, Laurens B, Lefaucheur R, Mariani LL, Marques A, Marse C, Ory-Magne F, Rigalleau V, Salhi H, Saubion A, Stott SRW, Thalamas C, Thiriez C, Tir M, Wyse RK, Benard A, Rascol O; LIXIPARK Study Group. Trial of Lixisenatide in Early Parkinson's Disease. N Engl J Med. 2024 Apr 4;390(13):1176-1185. doi: 10.1056/NEJMoa2312323.

  PMID: 38598572 BACKGROUND

• Lincoff AM, Brown-Frandsen K, Colhoun HM, Deanfield J, Emerson SS, Esbjerg S, Hardt-Lindberg S, Hovingh GK, Kahn SE, Kushner RF, Lingvay I, Oral TK, Michelsen MM, Plutzky J, Tornoe CW, Ryan DH; SELECT Trial Investigators. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023 Dec 14;389(24):2221-2232. doi: 10.1056/NEJMoa2307563. Epub 2023 Nov 11.

  PMID: 37952131 BACKGROUND

• Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar 18;384(11):989-1002. doi: 10.1056/NEJMoa2032183. Epub 2021 Feb 10.

  PMID: 33567185 BACKGROUND

• Fitzgerald KC, Salter A, Tyry T, Fox RJ, Cutter G, Marrie RA. Measures of general and abdominal obesity and disability severity in a large population of people with multiple sclerosis. Mult Scler. 2020 Jul;26(8):976-986. doi: 10.1177/1352458519845836. Epub 2019 May 13.

  PMID: 31079537 BACKGROUND

• Hedstrom AK, Brenner N, Butt J, Hillert J, Waterboer T, Olsson T, Alfredsson L. Overweight/obesity in young adulthood interacts with aspects of EBV infection in MS etiology. Neurol Neuroimmunol Neuroinflamm. 2020 Dec 15;8(1):e912. doi: 10.1212/NXI.0000000000000912. Print 2021 Jan.

  PMID: 33465039 BACKGROUND

• Mandato C, Colucci A, Lanzillo R, Staiano A, Scarpato E, Schiavo L, Operto FF, Serra MR, Di Monaco C, Napoli JS, Massa G, Vajro P. Multiple Sclerosis-Related Dietary and Nutritional Issues: An Updated Scoping Review with a Focus on Pediatrics. Children (Basel). 2023 Jun 7;10(6):1022. doi: 10.3390/children10061022.

  PMID: 37371254 BACKGROUND

• Lutfullin I, Eveslage M, Bittner S, Antony G, Flaskamp M, Luessi F, Salmen A, Gisevius B, Klotz L, Korsukewitz C, Berthele A, Groppa S, Then Bergh F, Wildemann B, Bayas A, Tumani H, Meuth SG, Trebst C, Zettl UK, Paul F, Heesen C, Kuempfel T, Gold R, Hemmer B, Zipp F, Wiendl H, Lunemann JD; German Competence Network Multiple Sclerosis (KKNMS). Association of obesity with disease outcome in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2023 Jan;94(1):57-61. doi: 10.1136/jnnp-2022-329685. Epub 2022 Nov 1.

  PMID: 36319190 BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis; Obesity; Weight Loss; Body Weight; Overweight

Interventions

Glucagon-Like Peptide 1; ocrelizumab

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Body Weight Changes

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Farrah J Mateen

  Northwestern University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dylan Rice, BA

CONTACT

240-362-4800; dylan.rice@northwestern.edu

Caroline Gebczak, BS

CONTACT

630-313-0470; caroline.gebczak@northwestern.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology

Study Record Dates

• First Submitted: September 17, 2025
• First Posted: October 3, 2025
• Study Start: November 15, 2025
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): August 31, 2028
• Last Updated: March 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)